One stage in the palatal fusion process is epithelial autolysis. One objective of this proposal, is to probe the mechanism underlying this event. To accomplish this, I propose to study the abnormal breakdown process induced by the drug hadacidin. Previous studies have shown that this teratogen blocks the de novo synthesis of AMP by inhibiting the enzyme adenylosuccinate synthetase. Experiments are planned to determine the biological and biochemical basis for hadacidin action. I propose to study the effects of hadacidin on cell growth and division, using cultures of the eukaryotic microorganism Dictyostelium discoideum grown in axenic medium and to determine if the inhibition of this purine metabolic pathway alters the physiological state of these cells. Biochemical and enzymatic procedures will be employed to isolate and purify the adenylosuccinate synthetase and adenylosuccinate activities involved in AMP formation and to determine if they are developmentally regulated enzymes and, if the activity of either enzyme changes following hadacidin treatment. I also propose to determine if hadacidin treated cells can undergo differentiation even in the presence of a food source. Finally, I propose to use the D. discoideum in a bioassay to determine if cAMP is secreted by palatal mesenchymal cells just prior to the time of epithelial autolysis.